Efficacy of curcumin and resveratrol in the synergistic activation of foetal haemoglobin in sickle cell disease
Robby Kumar, Eli MohapatraBackground and objectives
Sickle cell disease is a major haemoglobin disorder, and foetal haemoglobin (HbF) remains the strongest modifier of disease severity. Hydroxyurea is the standard HbF-inducing drug, but many patients show limited response. Curcumin and resveratrol are natural polyphenols with low toxicity. This study evaluated their individual and combined effects on HbF induction in K562 cells and primary CD34⁺ cells.
Methods
K562 cells were treated with curcumin, resveratrol, and hydroxyurea at increasing doses. Viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and IC₅₀ values (half maximal inhibitory concentration) were calculated. Drug combinations were tested in fixed ratios, and synergy was analysed using CompuSyn and SynergyFinder. CD34⁺ cells were isolated by MACS (magnetic-activated cell sorting) and differentiated for 14 days. Treatments began on day 3, and HbF levels were measured by ELISA.
Results
Curcumin showed the lowest IC₅₀ (74.8–66.3 µM), followed by resveratrol (84.3–75.2 µM), and hydroxyurea (140–131.9 µM) ( p< 0.05 for all comparisons). All compounds maintained over 70% viability at sub-IC₅₀ doses in both K562 and CD34⁺ cells. The strongest synergy was observed in the curcumin + resveratrol combination (Combination index (CI) 0.55±0.03; Loewe score 39.7±3.1), indicating a strong synergistic interaction despite model-specific differences. HbF induction followed the same trend and was consistent across experimental replicates. Curcumin raised HbF to 16.8% (1.9-fold), resveratrol to 12.5% (1.4-fold), and hydroxyurea to 21.2% (2.3-fold). Curcumin + resveratrol showed the highest induction at 24.92% (2.7-fold). In SCD CD34⁺ cells, the same combination produced 27.8% relative to untreated baseline.
Interpretation and conclusions
The strong synergy reflects the complementary action of antioxidant, epigenetic, and nitric-oxide–linked pathways. Minimal HbF rise in normal CD34⁺ cells indicate disease-specific responsiveness. Curcumin and resveratrol together form a potent and safe strategy for enhancing HbF and may serve as an effective adjunct therapy for SCD.